柠檬酸解离钛配位络合药物在4AA制备中的应用

Application of Citric Acid Dissociated Titanium Coordination Complex in 4AA Preparation

四氯化钛作为反应物,在(3R,4R)-3-[(R)-1-叔丁基二甲基硅氧乙基]-4-乙酰氧基-2-氮杂环丁酮(4AA)合成过程中参与成环反应,钛离子与产物也容易形成络合。在pH<4的醇溶液中,柠檬酸竞争配位钛离子,将产物解离进入有机相。通过单因素试验筛选醇溶剂为异丙醇,可选择(1+1)盐酸或磷酸调节pH至4以下,结果显示最佳解离条件为:40%柠檬酸溶液48.0g;异丙醇浓度为0.5%,用量200mL;反应时间30min;解离产物收率76.7%。

Titanium tetrachloride,as a reactant,takes part in the cyclization reaction during the synthesis of 4AA,and titanium ion and the product are easy to form complexation.In the alcohol solution with pH<4,citric acid competes for the coordination of titanium ion and dissociates the product into the organic phase.Through single factor test,isopropanol is selected as the alcohol solvent,and(1+1)hydrochloric acid or phosphoric acid can be selected to adjust the pH below 4.The best dissociation conditions are:48.0g 40%citric acid solution;0.5%isopropanol,200mL dosage,30min reaction time,and 76.7%yield of dissociation products.